2-week dc of MTX and Influenza Vaccination in RA (2 wk MTX)

October 26, 2016 updated by: Eun Bong Lee, Seoul National University Hospital

Effect of Two-week Discontinuation of Methotrexate on Efficacy of Seasonal Influenza Vaccination in Patients With Rheumatoid Arthritis: A Randomized Clinical Trial

To investigate whether a transient discontinuation of methotrexate MTX for 2 weeks improves the vaccination response to a seasonal influenza.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that affects the joints as the main target of the inflammation. Patients with RA require chronic treatment with disease modifying antirheumatic drugs (DMARDs) including methotrexate (MTX), which constitutes the mainstay of treatment. Underlying immune dysfunction and the additional immune suppression associated with treatment render patients with RA more susceptible to infection. Thus, vaccination of the preventive diseases is crucial and recommended in all patients unless contraindicated.

However, low dose of glucocorticoids, conventional DMARDs and biological DMARDs including tumor necrosis factor inhibitors have been reported to substantially decrease vaccine response (4); MTX has been reported to be associated with a decreased response to seasonal influenza vaccination by up to 15%.

To optimize a vaccine response, vaccination should be administrated before the treatment with immunesuppressive medications is initiated. However, most patients with RA are already on stable dose of MTX at the time of when vaccinations. To improve the vaccine response, a short term discontinuation of MTX could be considered. In a prior study, we discovered that a temporary discontinuation of MTX for 4 weeks during peri-vaccination period tended to be associated with an improved response to vaccination with trivalent influenza vaccination (Figure 1). It remains to be defined whether MTX discontinuation for shorter period increases the vaccination efficacy while minimizing the RA flare rate.

Study Type

Interventional

Enrollment (Anticipated)

318

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 110-744
        • Recruiting
        • Seoul National University Hospital
        • Contact:
      • Seoul, Korea, Republic of, 156-707
        • Recruiting
        • SMG-SNU Boramae Medical Center
        • Contact:
        • Principal Investigator:
          • Kichul Shin, MD PhD
    • Gyeonggi-do
      • Bundang, Gyeonggi-do, Korea, Republic of, 463-870
        • Recruiting
        • Seoul National Univ. Bundang Hospital
        • Contact:
        • Principal Investigator:
          • Yun Jong Lee, MD PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males or females ≥ 19 years and < 65 years of age at time of consent
  • Have a diagnosis of RA per ACR criteria
  • Must understand and voluntarily sign an informed consent form including writing consent for data protection
  • Stable doses of methotrexate over the preceding 6 weeks

Exclusion Criteria:

  • Pregnant or lactating females
  • Previous anaphylactic response to vaccine components or to egg.
  • Acute infection with T >38°C at the time of vaccination
  • History of Guillain-Barre syndrome or demyelinating syndromes
  • Previous vaccination with any live vaccine 4 weeks before or any inactivated vaccine 2 weeks before the study
  • Blood transfusion within 6 months
  • Active rheumatoid arthritis necessitating a recent change in the drug regimen
  • Any other rheumatic disease such as systemic lupus erythematosus, mixed connective tissue disease, dermatomyositis/polymyositis, and vasculitis except for secondary Sjogren's disease
  • Any condition including laboratory abnormality which places the subject at unacceptable risk
  • Subjects who decline to participate

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
SHAM_COMPARATOR: Group 1: MTX continue
Group will continue MTX after vaccination
Drug: Methotrexate
EXPERIMENTAL: Group 2: MTX hold
will hold MTX for 2 weeks after vaccination
Drug: Methotrexate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of satisfactory vaccine response
Time Frame: 4 weeks
Proportion of satisfactory vaccine response that is defined as ≥ 4-fold increase in post-vaccination titer in ≥ 2 of 4 influenza strains
4 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion of patients who have ≥ 4-fold increase in post-vaccination titer in ≥ 3 of 4 influenza strains
Time Frame: 4 weeks
4 weeks
Proportion of seroprotection for each strain
Time Frame: 4 weeks
4 weeks
Change from baseline in titer (in GMT) for each strain
Time Frame: 4 weeks
4 weeks
Change from baseline in DAS28-4 (CRP) at 4 weeks after vaccination
Time Frame: 4 weeks
4 weeks
Proportion of patients who experience increase in disease activity
Time Frame: 4 weeks
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seoul National University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2016

Primary Completion (ANTICIPATED)

August 1, 2017

Study Completion (ANTICIPATED)

August 1, 2017

Study Registration Dates

First Submitted

September 7, 2016

First Submitted That Met QC Criteria

September 7, 2016

First Posted (ESTIMATE)

September 12, 2016

Study Record Updates

Last Update Posted (ESTIMATE)

October 27, 2016

Last Update Submitted That Met QC Criteria

October 26, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SNUH-IMJ-003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Rheumatoid Arthritis

Clinical Trials on Methotrexate

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Israel

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe